Research

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13 pages, 2225 KiB

Open AccessArticle

Yield of FDG PET/CT for Defining the Extent of Disease in Patients with Kaposi Sarcoma

by Louise Pesqué, Julie Delyon, Coralie Lheure, Barouyr Baroudjian, Maxime Battistella, Pascal Merlet, Céleste Lebbé and Laetitia Vercellino

Cancers 2022, 14(9), 2189; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14092189 - 27 Apr 2022

Cited by 4 | Viewed by 2031

Abstract

Background: Positron emission tomography/computed tomography with fluorodeoxyglucose (F-18) (FDG PET/CT) is increasingly used in Kaposi sarcoma (KS), but its value has not been assessed. Objectives: In this study, we aimed to evaluate the diagnostic accuracy of FDG PET/CT to define the extent of [...] Read more.

Background: Positron emission tomography/computed tomography with fluorodeoxyglucose (F-18) (FDG PET/CT) is increasingly used in Kaposi sarcoma (KS), but its value has not been assessed. Objectives: In this study, we aimed to evaluate the diagnostic accuracy of FDG PET/CT to define the extent of disease in KS. Methods: Consecutive patients with KS referred to our department for FDG PET/CT were included. The diagnostic accuracy of FDG PET/CT for cutaneous and extra-cutaneous KS staging was assessed on a per lesion basis compared to staging obtained from clinical examination, standard imaging, endoscopy, histological analyses, and follow-up. Results: From 2007 to 2017, 75 patients with FDG PET/CT were analyzed. The sensitivity and specificity of FDG PET/CT for the overall detection of KS lesions were 71 and 98%, respectively. Sensitivity and specificity were 100 and 85% for lymph nodes, 87 and 98% for bone, 87 and 100% for lungs, and 100 and 100% for muscle involvement, whereas sensitivity was only 17% to detect KS digestive involvement. The sensitivity of the diagnostic for KS cutaneous involvement increased from 73 to 88% when using a whole-body examination. Conclusion: FDG PET/CT showed good sensitivity and specificity for KS staging (digestive involvement excepted) and could be used for staging patients with active KS. Full article

(This article belongs to the Special Issue Rare Skin Cancers: Recent Advances in Classification and Management)

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23 pages, 15855 KiB

Open AccessArticle

Organotypic Epithelial Raft Cultures as a Three-Dimensional In Vitro Model of Merkel Cell Carcinoma

by Arturo Temblador, Dimitrios Topalis, Joost van den Oord, Graciela Andrei and Robert Snoeck

Cancers 2022, 14(4), 1091; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14041091 - 21 Feb 2022

Cited by 3 | Viewed by 2562

Abstract

Merkel cell carcinoma (MCC) is a rare type of skin cancer for which an in vitro model is still lacking. MCC tumorigenesis is associated either with the integration of Merkel cell polyomavirus into the host genome, or with the accumulation of somatic mutations [...] Read more.

Merkel cell carcinoma (MCC) is a rare type of skin cancer for which an in vitro model is still lacking. MCC tumorigenesis is associated either with the integration of Merkel cell polyomavirus into the host genome, or with the accumulation of somatic mutations upon chronic exposure to UV light. Transgenic animals expressing the viral oncoproteins, which are constitutively expressed in virus-related MCC, do not fully recapitulate MCC. Although cell-line-derived xenografts have been established for the two subtypes of MCC, they still present certain limitations. Here, we generated organotypic epithelial raft cultures (OERCs) of MCC by using primary human keratinocytes and both virus-positive and virus-negative MCC cell lines. The primary human keratinocytes and the tumor cells were grown on top of a dermal equivalent. Histological and immunohistochemical examination of the rafts confirmed the growth of MCC cells. Furthermore, gene expression analysis revealed differences in the expression profiles of the distinct tumor cells and the keratinocytes at the transcriptional level. In summary, considering the limited availability of patient samples, OERCs of MCC may constitute a suitable model for evaluating the efficacy and selectivity of new drug candidates against MCC; moreover, they are a potential tool to study the oncogenic mechanisms of this malignancy. Full article

(This article belongs to the Special Issue Rare Skin Cancers: Recent Advances in Classification and Management)

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14 pages, 22041 KiB

Open AccessArticle

Treatment of Malignant Adnexal Tumors of the Skin: A 12-Year Perspective

by Marcin Kleibert, Iga Płachta, Anna M. Czarnecka, Mateusz J. Spałek, Anna Szumera-Ciećkiewicz and Piotr Rutkowski

Cancers 2022, 14(4), 998; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14040998 - 16 Feb 2022

Cited by 3 | Viewed by 6589

Abstract

Malignant adnexal cancers of the skin—extremely rare neoplasms—are mostly reported as non-symptomatic, slow-growing nodules. These carcinomas occur mainly in the middle-aged (50–60 years of age); they are mostly localized on the upper part of the body and are locally aggressive, infiltrate surrounding tissue, [...] Read more.

Malignant adnexal cancers of the skin—extremely rare neoplasms—are mostly reported as non-symptomatic, slow-growing nodules. These carcinomas occur mainly in the middle-aged (50–60 years of age); they are mostly localized on the upper part of the body and are locally aggressive, infiltrate surrounding tissue, and metastasize to regional lymph nodes. The patients’ outcomes depend on multiple prognostic factors, including the size of the primary tumor and its mitotic count. Surgical resection of the primary tumor with or without regional lymph nodes is the treatment method of choice; however, due to aggressive tumor behavior, perioperative treatment may be considered. The role and efficacy of radiotherapy in the treatment of skin adnexal malignancies are not yet fully defined. Some authors suggest that adjuvant radiotherapy may be considered in locally advanced and regional disease. The aim of this study was to evaluate treatment outcomes and assess the efficacy of combined therapy in patients with adnexal malignancies. Our analysis covered all cases of cutaneous adnexal tumor patients diagnosed and provided with multidisciplinary treatment with surgery and radiotherapy since the beginning of 2009. Full article

(This article belongs to the Special Issue Rare Skin Cancers: Recent Advances in Classification and Management)

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13 pages, 2944 KiB

Open AccessArticle

NGS-Based Analysis of Atypical Deep Penetrating Nevi

by Antonella Manca, Maria Cristina Sini, Anna Maria Cesinaro, Francesca Portelli, Carmelo Urso, Maria Lentini, Roberta Cardia, Llucia Alos, Martin Cook, Sara Simi, Panagiotis Paliogiannis, Vincenzo De Giorgi, Antonio Cossu, Giuseppe Palmieri and Daniela Massi

Cancers 2021, 13(12), 3066; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13123066 - 19 Jun 2021

Cited by 10 | Viewed by 2348

Abstract

Deep penetrating nevi (DPNs) are rare melanocytic neoplasms consisting of pigmented spindled or epithelioid melanocytes with a distinctive wedge-shaped configuration showing activation of the WNT pathway, with unusual cyto-architectural features. It is unclear whether they show a distinct genomic profile associated with a [...] Read more.

Deep penetrating nevi (DPNs) are rare melanocytic neoplasms consisting of pigmented spindled or epithelioid melanocytes with a distinctive wedge-shaped configuration showing activation of the WNT pathway, with unusual cyto-architectural features. It is unclear whether they show a distinct genomic profile associated with a diverse metastatic potential. We describe herein a cohort of 21 atypical DPNs analyzed by next-generation sequencing using the Ion AmpliSeq™ Comprehensive Cancer Panel. We found that β-catenin exon 3 was mutated in 95% and MAP kinase pathway genes in 71% of the cases. Less frequent mutations were observed in HRAS (19%) and MAP2K1 (24%). Isocitrate dehydrogenases 1 (IDH1) mutations, including R132C, V178I, and S278L, were identified in 38% of cases and co-existed with BRAF/HRAS mutations. The only case with progressive nodal disease carried alterations in the β-catenin pathway and mutations in IDH1 and NRAS (codon 61). By a comprehensive mutation analysis, we found low genetic heterogeneity and a lack of significant associations between specific gene mutations and histopathological features, despite atypical features. Whether the acquisition of an NRAS or IDH1 mutation in an atypical DPN may represent a molecular evolution implying a pathway to melanoma progression should be confirmed in a larger series. Full article

(This article belongs to the Special Issue Rare Skin Cancers: Recent Advances in Classification and Management)

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11 pages, 723 KiB

Open AccessArticle

Long-Term Outcome of Neoadjuvant Tyrosine Kinase Inhibitors Followed by Complete Surgery in Locally Advanced Dermatofibrosarcoma Protuberans

by Jessica Beaziz, Maxime Battistella, Julie Delyon, Cécile Farges, Oren Marco, Cécile Pages, Christine Le Maignan, Laetitia Da Meda, Nicole Basset-Seguin, Matthieu Resche-Rigon, Anouk Walter Petrich, Delphine Kérob, Céleste Lebbé and Barouyr Baroudjian

Cancers 2021, 13(9), 2224; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13092224 - 06 May 2021

Cited by 8 | Viewed by 2305

Abstract

In locally advanced dermatofibrosarcoma protuberans (DFSP), imatinib mesylate has been described as an efficient neoadjuvant therapy. This retrospective study included patients with locally advanced DFSP who received neoadjuvant TKI (imatinib or pazopanib) from 2007 to 2017 at Saint Louis Hospital, Paris. The primary [...] Read more.

In locally advanced dermatofibrosarcoma protuberans (DFSP), imatinib mesylate has been described as an efficient neoadjuvant therapy. This retrospective study included patients with locally advanced DFSP who received neoadjuvant TKI (imatinib or pazopanib) from 2007 to 2017 at Saint Louis Hospital, Paris. The primary endpoint was the evaluation of the long-term status. A total of 27 patients were included, of whom nine had fibrosarcomatous transformation. The median duration of treatment was 7 months. The best response to TKI treatment before surgery, evaluated according to RECIST1.1 on MRI, consisted of complete/partial response (38.5%) or stability (46.2%). DFSP was surgically removed in 24 (89%) patients. A total of 23 patients (85%) were disease-free after 64.8 months of median follow-up (95% confidence interval 47.8; 109.3). One patient developed distant metastases 37 months after surgical tumor resection and finally died. Two patients (7%) did not get surgery because of metastatic progression during TKI treatment, and one patient refused surgery even though the tumor decreased by 30%. Treatment-related adverse events (AE) occurred in 23 patients (85%). Only four patients (imatinib: n = 3, pazopanib: n = 1) had grade ≥3 AE requiring temporary treatment disruption. Neoadjuvant TKI followed by complete surgery with micrographic analysis is an effective strategy for locally advanced and unresectable DFSP, with durable local recurrence disease-free survival. Full article

(This article belongs to the Special Issue Rare Skin Cancers: Recent Advances in Classification and Management)

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14 pages, 2440 KiB

Open AccessArticle

Merkel Cell Carcinoma of Unknown Primary: Immunohistochemical and Molecular Analyses Reveal Distinct UV-Signature/MCPyV-Negative and High Immunogenicity/MCPyV-Positive Profiles

by Piotr Donizy, Joanna P. Wróblewska, Dora Dias-Santagata, Katarzyna Woznica, Przemyslaw Biecek, Mark C. Mochel, Cheng-Lin Wu, Janusz Kopczynski, Malgorzata Pieniazek, Janusz Ryś, Andrzej Marszalek and Mai P. Hoang

Cancers 2021, 13(7), 1621; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13071621 - 31 Mar 2021

Cited by 11 | Viewed by 2100

Abstract

Background: Merkel cell carcinomas of unknown primary (MCC-UPs) are defined as deep-seated tumors without an associated cutaneous tumor. Although the distinction has important clinical implications, it remains unclear whether these tumors represent primary tumors of lymph nodes or metastatic cutaneous primaries. Methods: We [...] Read more.

Background: Merkel cell carcinomas of unknown primary (MCC-UPs) are defined as deep-seated tumors without an associated cutaneous tumor. Although the distinction has important clinical implications, it remains unclear whether these tumors represent primary tumors of lymph nodes or metastatic cutaneous primaries. Methods: We compared the immunohistochemical profiles of four groups of MCCs (Merkel cell polyomavirus (MCPyV)-positive UP, MCPyV-negative UP, MCPyV-positive known primary (KP), and MCPyV-negative KP) using B-cell and pre-B-cell markers, cell cycle regulating proteins, follicular stem cell markers, and immune markers, and performed next generation and Sanger sequencing. Results: Virus-positive and virus-negative MCC-UPs exhibited an immunoprofile similar to virus-positive and virus-negative primary cutaneous MCCs, respectively. MCC-UP tumors (both virus-positive and -negative) were immunogenic with similar or even higher tumoral PD-L1 expression and intratumoral CD8 and FoxP3 infiltrates in comparison to MCPyV-positive cutaneous tumors. In addition, similar to primary cutaneous MCCs, MCPyV-negative MCC-UPs exhibited UV signatures and frequent high tumor mutational burdens, whereas few molecular alterations were noted in MCPyV-positive MCC-UPs. Conclusions: Our results showed distinct UV-signatures in MCPyV-negative tumors and high immunogenicity in MCPyV-positive tumors. Although additional studies are warranted for the MCPyV-positive cases, our findings are supportive of a cutaneous metastatic origin for MCPyV-negative MCC-UP tumors. Full article

(This article belongs to the Special Issue Rare Skin Cancers: Recent Advances in Classification and Management)

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Review

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36 pages, 9062 KiB

Open AccessReview

Malignant Superficial Mesenchymal Tumors in Children

by Philippe Drabent and Sylvie Fraitag

Cancers 2022, 14(9), 2160; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14092160 - 26 Apr 2022

Cited by 1 | Viewed by 3779

Abstract

Malignant superficial mesenchymal tumors are a very diverse group of neoplasms with few clinical and radiological discriminatory factors. Hence, some of these cancers are rarely suspected based on clinical and radiological grounds, others may be easily misdiagnosed, and the histological analysis of a [...] Read more.

Malignant superficial mesenchymal tumors are a very diverse group of neoplasms with few clinical and radiological discriminatory factors. Hence, some of these cancers are rarely suspected based on clinical and radiological grounds, others may be easily misdiagnosed, and the histological analysis of a biopsy or resection is central in the diagnostic process. In children, the age at presentation is a major element of the differential diagnosis. Some tumors have a very distinct epidemiology, while others may be seen at any age. More recently, the advances in molecular biology have greatly improved the diagnosis of mesenchymal tumors and new entities are still being described. In the present review, we provide an overview of the diversity of malignant superficial mesenchymal tumors in children, including new and/or rare entities. We discuss the important diagnostic features, be they clinical, histological, or molecular. Special attention was given to the genetic features of these tumors, particularly when they were helpful for the diagnosis or treatment. Full article

(This article belongs to the Special Issue Rare Skin Cancers: Recent Advances in Classification and Management)

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19 pages, 1780 KiB

Open AccessReview

Antibody–Drug Conjugates as an Emerging Therapy in Oncodermatology

by Clara Esnault, David Schrama, Roland Houben, Serge Guyétant, Audrey Desgranges, Camille Martin, Patricia Berthon, Marie-Claude Viaud-Massuard, Antoine Touzé, Thibault Kervarrec and Mahtab Samimi

Cancers 2022, 14(3), 778; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030778 - 02 Feb 2022

Cited by 12 | Viewed by 4155

Abstract

Antibody–drug conjugates (ADCs) are an emerging class of therapeutics, with twelve FDA- and EMA-approved drugs for hematological and solid cancers. Such drugs consist in a monoclonal antibody linked to a cytotoxic agent, allowing a specific cytotoxicity to tumor cells. In recent years, tremendous [...] Read more.

Antibody–drug conjugates (ADCs) are an emerging class of therapeutics, with twelve FDA- and EMA-approved drugs for hematological and solid cancers. Such drugs consist in a monoclonal antibody linked to a cytotoxic agent, allowing a specific cytotoxicity to tumor cells. In recent years, tremendous progress has been observed in therapeutic approaches for advanced skin cancer patients. In this regard, targeted therapies (e.g., kinase inhibitors) or immune checkpoint-blocking antibodies outperformed conventional chemotherapy, with proven benefit to survival. Nevertheless, primary and acquired resistances as well as adverse events remain limitations of these therapies. Therefore, ADCs appear as an emerging therapeutic option in oncodermatology. After providing an overview of ADC design and development, the goal of this article is to review the potential ADC indications in the field of oncodermatology. Full article

(This article belongs to the Special Issue Rare Skin Cancers: Recent Advances in Classification and Management)

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25 pages, 3113 KiB

Open AccessReview

Recent Advances on Immunohistochemistry and Molecular Biology for the Diagnosis of Adnexal Sweat Gland Tumors

by Nicolas Macagno, Pierre Sohier, Thibault Kervarrec, Daniel Pissaloux, Marie-Laure Jullie, Bernard Cribier and Maxime Battistella

Cancers 2022, 14(3), 476; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030476 - 18 Jan 2022

Cited by 19 | Viewed by 6448

Abstract

Cutaneous sweat gland tumors are a subset of adnexal neoplasms that derive or differentiate into the sweat apparatus. Their great diversity, rarity, and complex terminology make their pathological diagnosis challenging. Recent findings have revealed a wide spectrum of oncogenic drivers, several of which [...] Read more.

Cutaneous sweat gland tumors are a subset of adnexal neoplasms that derive or differentiate into the sweat apparatus. Their great diversity, rarity, and complex terminology make their pathological diagnosis challenging. Recent findings have revealed a wide spectrum of oncogenic drivers, several of which are of diagnostic interest for pathologists. Most of these molecular alterations are represented by gene fusions, which are shared with other homologous neoplasms occurring in organs containing exocrine glands, such as salivary and breast glands, which show similarities to the sweat apparatus. This review aims to provide a synthesis of the most recent immunohistochemical and molecular markers used for the diagnosis of sweat gland tumors and to highlight their relationship with similar tumors in other organs. It will cover adenoid cystic carcinoma (NFIB, MYB, and MYBL1 fusion), cutaneous mixed tumor (PLAG1 fusion), cylindroma and spiradenoma and their carcinomas thereof (NF-κB activation through CYLD inactivation or ALKP1 hotspot mutation), hidradenoma and hidradenocarcinoma (MAML2 fusion), myoepithelioma (EWSR1 and FUS fusion), poroma and porocarcinoma (YAP1, MAML2, and NUTM1 fusion), secretory carcinoma (ETV6, NTRK3 fusion), tubular adenoma and syringo-cystadenoma papilliferum (HRAS and BRAF activating mutations). Sweat gland tumors for which there are no known molecular abnormalities will also be briefly discussed, as well as potential future developments. Full article

(This article belongs to the Special Issue Rare Skin Cancers: Recent Advances in Classification and Management)

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